title: Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior.
abstract: NMDA receptors are activated after binding of the agonist glutamate to the NR2 subunit along with a co-agonist, either L-glycine or D-serine, to the NR1 subunit. There is substantial evidence to suggest that D-serine is the most relevant co-agonist in forebrain regions and that alterations in D-serine levels contribute to psychiatric disorders. D-serine is produced through isomerization of L-serine by serine racemase (Srr), either in neurons or in astrocytes. It is released by astrocytes by an activity-dependent mechanism involving secretory vesicles. In the present study we generated transgenic mice (SrrTg) expressing serine racemase under a human GFAP promoter. These mice were biochemically and behaviorally analyzed using paradigms of anxiety, depression and cognition. Furthermore, we investigated the behavioral effects of long-term administration of D-serine added to the drinking water. Elevated brain D-serine levels in SrrTg mice resulted in specific behavioral phenotypes in the forced swim, novelty suppression of feeding and olfactory bulbectomy paradigms that are indicative of a reduced proneness towards depression-related behavior. Chronic dietary D-serine supplement mimics the depression-related behavioral phenotype observed in SrrTg mice. Our results suggest that D-serine supplementation may improve mood disorders.
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.
authors.forename: David-Marian
authors.initials: DM
authors.lastname: Otte
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Barcena de Arellano
authors.forename: Andras
authors.initials: A
authors.lastname: Bilkei-Gorzo
authors.forename: Onder
authors.initials: O
authors.lastname: Albayram
authors.forename: Sophie
authors.initials: S
authors.lastname: Imbeault
authors.forename: Haang
authors.initials: H
authors.lastname: Jeung
authors.forename: Judith
authors.initials: J
authors.lastname: Alferink
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000493:pharmacokinetics / Q000494:pharmacology; D000099300:Serine Racemase
chemical_list: D005904:Glial Fibrillary Acidic Protein; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase